The primary goal of this research is to use cultured animal cells as a model system to elucidate basic genetic processes especially the genetic control of metabolism in man. A variety of biochemical mutants affecting carbohydrate, amino acid, pyrimidine and purine metabolism in Chinese hamster cells in culture have been isolated and characterized. The first group of mutants are resistant to deoxygalactose and deficient in galactokinase activity. The frequency of mutation increases after chemical mutagenesis and the resistant phenotype has persisted in the absence of selection. The second group of mutants are those pleiotropic for carbohydrate metabolism we reported previously (Chu et al., PNAS 69, 3459, 1972; Chu, Genetics 78, 115, 1974; Sun et al., PNAS 72, 469, 1975). Recent biochemical characterization of the representative members of mutants belonging to different complementation groups indicate that they may be mutations in a structural or regulatory gene locus which affects either a critic acid cycle enzyme, a component of the electron transport chain, or oxidative phosphorylation. The third group of mutants are those resistant to amino acid analogues or high concentrations of native amino acids. Those mutants characterized so far appear to show defects in amino acid transport systems. Finally, we have isolated mutants that are resistant to adenine and adenosine and exhibit high intracellular PRPP levels, possibly as a result of an altered PRPP synthetase that is resistant to feedback inhibition.